title: Metabolite profiling and identification of triptolide in rats.
abstract: The purpose of the current study was to investigate the metabolite profile of [(3)H]triptolide in rats. The separation and characterisation techniques used to identify the major metabolites were high-performance liquid chromatography-online radiodetector, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and nuclear magnetic resonance. In all, 33 major metabolites were detected. The major components found in the rat plasma included the parent drug and its monohydroxy- and dihydroxy-metabolites. Reference standards for the monohydroxy-metabolites were obtained either by the incubation of the parent drug with rat liver microsomes or by microbial transformation with Cunninghamella blakesleana. The metabolites' structures were identified as 17-hydroxytriptolide, 16-hydroxytriptolide, tripdiolide, and 15-hydroxytriptolide. The major metabolites found in male rat urine included the monohydroxy-, dihydroxy-, and trihydroxy-metabolites. The major metabolites in female rat urine were the monohydroxy- and dihydroxy-metabolites, as well as sulphates of the monohydroxy-metabolites. A glutathione adduct, multiple hydroxy-metabolites, and a number of unidentified metabolites were detected in the bile and faeces of male rats. Sulphates of monohydroxy-metabolites were detected in the bile and faeces of female rats.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.forename: Haihua
authors.initials: H
authors.lastname: Huang
authors.forename: Shunbo
authors.initials: S
authors.lastname: Zhao
authors.forename: Xiuli
authors.initials: X
authors.lastname: Li
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004224:Diterpenes / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D004852:Epoxy Compounds / Q000032:analysis / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D005243:Feces / Q000737:chemistry; D005260:Female; D057230:Limit of Detection; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D010616:Phenanthrenes / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide
keywords: High-performance liquid chromatography-online radiodetector; Metabolite profiling; Triptolide; Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry